Artigos e Materiais de Revistas Científicas - LIM/55
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- Lower urinary tract dysfunction in uncommon neurological diseases, Part II: A report of the Neuro-urology Promotion Committee of the International Continence Society(2023) SINHA, S.; WACHTER, S. De; WELK, B.; SAKAKIBARA, R.; VRIJENS, D. M. J.; KONSTANTINIDIS, C.; RAPIDI, C.-A.; MONTEIRO, L. M.; GOMES, C. M.; DRAKE, M. J.; HAMID, R.This is the second manuscript from the Neuro-urology Promotion Committee of the International Continence Society (ICS) discussing uncommon neuro-urological conditions that are not well described in urological literature. Readers are referred to the first document for a more detailed understanding of how neurological disease might affect lower urinary tract function ( https://doi.org/10.1016/j.cont.2022.100022). Eleven conditions are covered. This includes five genetic conditions — Duchene muscular dystrophy, mitochondrial encephalopathy, Down's syndrome, adrenoleukodystrophy and Ochoa's syndrome. Three infection-associated conditions are covered including central nervous system tuberculosis, schistosomal myeloradiculopathy and post-polio syndrome. Three other conditions covered are myasthenia gravis, syringomyelia and the vegetative state. Key aspects and specific recommendations related to clinical practice are summarized in tables. Knowledge of unusual neurological conditions that can affect the lower urinary tract is important for ensuring a timely and precise diagnosis. This document from the ICS, along with Part I published earlier, can serve as a reference for clinicians presented with unusual forms of neurogenic lower urinary tract dysfunction.
- Recommendations and optimal approaches to robotic-assisted partial nephrectomy: A consensus of Brazilian experts(2023) FARIA, E. F.; MOSCHOVAS, M. C.; VAZ, C.; POMPEO, A.; SANTOS, A.; STIEVANO, A.; BERGER, A.; CARNEIRO, A.; DOURADO, A.; COLOMBO, J. R.; PASSEROTTI, C.; ANDREONI, C.; FRAGA, C.; GUGLIELMETTI, G.; LEMOS, G.; GUIMARãES, G.; NOGUEIRA, L.; ROCHA, M.; MELO, P.; ARANTES, P.; ROMANELLI, P.; TOURINHO, R.; NISHIMOTO, R.; MACHADO, R.; REIS, R.; FROTA, R.; GUIDA, R.; DUBEUX, V.; GUALBERTO, R.; TOBIAS-MACHADO, M.Objective: Robotic-assisted partial nephrectomy (RAPN) is established as the gold standard approach to treating small renal masses. However, numerous technical challenges and concepts related to this approach are still under discussion and are not consensus among surgeons from different centers. We performed an online questionnaire with multiple topics about RAPN and selected high-volume surgeons from referral centers in Brazil to achieve a consensus. Methods: We implemented an online consensus of 29 experts selected based on surgical expertise and competence in analyzing the published literature. Based on the collected literature and current Guidelines (NCCN, AUA, and EAU) we created a questionnaire with 131 questions and administered it to all participants. The statements and the Delphi technique design were combined in a single round of questions. The answers were reviewed, 70% of concordance was considered a consensus, and a final manuscript with recommendations was developed. Results: We divided our results into 25 subtopics that included all questions and discussions of the questionnaire, including preoperative settings, surgical technique, pathological analysis, technology use, and challenging cases. Some areas had limited data in the literature, and these potential limitations were addressed and discussed on each topic. Conclusion: RAPN is the standard surgical treatment for renal masses in the centers of robotic surgery. Among the important topics of this study, we recommend always performing the first RAPN cases with proctors’ assistance, conducting preoperative planning using good-quality imaging exams, minimizing the amount of renal parenchyma removed, and achieving appropriate hemostatic suture while reducing renal parenchyma ischemia.
- Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy(2022) SALTER, Carolyn A.; TIN, Amy L.; BERNIE, Helen L.; NASCIMENTO, Bruno; KATZ, Darren J.; BENFANTE, Nicole E.; CARLSSON, Sigrid V.; MULHALL, John P.Background: Prior studies suggest that men with good erectile function shortly after radical prostatectomy (RP) can subsequently have worsened erectile function. Aim: To determine the prevalence and predictors of early erectile function recovery post-RP and of worsening erectile function after initial erectile function recovery. Methods: We retrospectively queried our institutional database. Men who underwent RP during 2008-2017 and who completed the International Index of Erectile Function erectile function domain both pre-RP and serially post-RP, constituted the population. Functional erections were defined as International Index of Erectile Function (IIEF)-6 erectile function domain scores >= 24. We analyzed factors predicting functional erections at 3 months post-RP as well as factors predicting a decrease in functional erections between 3 and 6 months, defined as >= 2-point drop in the erectile function domain. Multivariable logistic regression models were used to identify predictors of early erectile function recovery and also of subsequent decline. Outcomes: Erectile function recovery rates at 3 months post-RP and predictive factors; rates of erectile function decline between 3-6 months and associated predictors. Results: Eligible patients comprised 1,655 men with median age of 62 (IQR 57, 67) years. Bilateral nerve-sparing (NS) surgery was performed in 71% of men, unilateral NS in 19%, and no NS in 10%. Of this population, 224 men (14%; 95% CI 12%, 15%) had functional erections at 3 months post-RP. On multivariable analysis, significant predictors of early erectile function recovery included: younger age (OR 0.93, P <.001), higher baseline erectile function domain score (OR 1.14, P <.001) and bilateral NS (OR 3.81, P =.002). The presence of diabetes (OR 0.43, P =.028) and a former smoking history (OR 0.63, P =.008; reference group: never smoker) was associated with the erectile dysfunction at 3 months post-RP. Of the men with early functional erections, 41% (95% CI 33%, 48%) had a >= 2-point decline in erectile function between 3 and 6 months. No factors were identified as predictors for this decline. Clinical Implications: Only a small proportion of men have functional erections at 3 months post-RP and a notable number of them will experience a decline in erectile function between 3 and 6 months. Strengths and Limitations: Strengths: large patient population and the use of validated questionnaire. Limitations: single-center retrospective study. Conclusion: A minority of men had functional erections 3 months post-RP, about half of whom had a decline in erectile function by month 6. We recommend appropriately counseling post-RP patients on the risk of such a
- Artificial cornea transplantation and visual rehabilitation: an integrative review(2024) FERNANDES, Tayna Meneses; ALVES, Mariana Cassiano; DINIZ, Caroline Oliveira; QUEIROZ, Guilherme Cunha; REIS, Sabrina T.Due to the development of complications and the biocompatibility and scarcity of transplant donor tissues, artificial corneas, which can be used for the rehabilitation of optical functions, have been developed. The current study aimed to analyze the visual rehabilitation effects of the Boston type I keratoprosthesis, Boston type II keratoprosthesis, Aurolab keratoprosthesis, osteo-odonto-keratoprosthesis, and tibial bone keratoprosthesis. Results showed that the Boston type I keratoprosthesis was the most effective for visual rehabilitation in patients with moist ocular surfaces. The Aurolab keratoprosthesis had a lower efficacy for visual rehabilitation. Nevertheless, it is still a viable option for individuals in economically restricted countries. In patients with dry eyes, the Boston type II keratoprosthesis was associated with the best visual rehabilitation. However, the final visual acuity of patients who received osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis implantation was not evaluated as the necessary information was not available.
- Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis(2023) LOPES-GONCALVES, Guilherme; COSTA-PESSOA, Juliana Martins; PIMENTA, Ruan; TOSTES, Ana Flavia; SILVA, Eloisa Martins da; LEDESMA, Felipe Lourenco; MALHEIROS, Denise Maria Avancini Costa; ZATZ, Roberto; THIEME, Karina; CAMARA, Niels Olsen Saraiva; OLIVEIRA-SOUZA, MariaFocal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome, which is characterized by podocyte injury. Given that the pathophysiology of nondiabetic glomerulosclerosis is poorly understood and targeted therapies to prevent glomerular disease are lacking, we decided to investigate the tight junction protein claudin-1 and the histone deacetylase sirtuin-1 (SIRT1), which are known to be involved in podocyte injury. For this purpose, we first examined SIRT1, claudin-1 and podocin expression in kidney biopsies from patients diagnosed with nondiabetic FSGS and found that upregulation of glomerular claudin-1 accompanies a significant reduction in glomerular SIRT1 and podocin levels. From this, we investigated whether a small molecule activator of SIRT1, SRT1720, could delay the onset of FSGS in an animal model of adriamycin (ADR)-induced nephropathy; 14 days of treatment with SRT1720 attenuated glomerulosclerosis progression and albuminuria, prevented transcription factor Wilms tumor 1 (WT1) downregulation and increased glomerular claudin-1 in the ADR + SRT1720 group. Thus, we evaluated the effect of ADR and/or SRT1720 in cultured mouse podocytes. The results showed that ADR [1 mu M] triggered an increase in claudin-1 expression after 30 min, and this effect was attenuated by pretreatment of podocytes with SRT1720 [5 mu M]. ADR [1 mu M] also led to changes in the localization of SIRT1 and claudin-1 in these cells, which could be associated with podocyte injury. Although the use of specific agonists such as SRT1720 presents some benefits in glomerular function, their underlying mechanisms still need to be further explored for therapeutic use. Taken together, our data indicate that SIRT1 and claudin-1 are relevant for the pathophysiology of nondiabetic FSGS.
- Diameter of ureteral access sheath and ureteral stenosis development: a systematic review(2023) PISSAIA, Tamires Battistini; BELKOVSKY, Mikhael; PASSEROTTI, Carlo Camargo; ARTIFON, Everton Luiz de Almeida; OTOCH, Jose Pinhata; CRUZ, Jose Arnaldo Shiomi daPurpose: Ureteral access sheaths (UAS) are widely used in ureteroscopy. UAS are believed to pose a significant risk for ureteral stenosis due to ureteral mucosal compression, but little evidence supports this claim. Our systematic review aimed to investigate the relationship between different UAS diameters and stenosis risk. Methods: A systematic search was conducted in PubMed, Embase, Web of Science, Scopus, and Cochrane, from its inception to May 2023. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines were followed. chi 2 test was performed to compare the prevalence within the groups. Results: Six nonrandomized trials and one randomized, with a total of 962 patients, were included. The overall incidence of ureteral stenosis of 0.9%. UAS sizes were: 9.5/11.5Fr, 10/12Fr, 11/13Fr, 12/14Fr, and 14/16Fr. Within each subgroup, the incidence of ureteral stenosis was: 0.4, 8, 0, 1, and 1% (p = 0.099). No trend for stenosis was observed among larger UAS. Conclusion: In this systematic review, no relationship between UAS diameter and incidence of ureteral stenosis was observed. Nonetheless, additional randomized controlled trials are required to support this finding.
- Complete Response to Sequential Human Epidermal Growth Factor Receptor 2-Targeted Strategies in a Heavily Pretreated Patient With Human Epidermal Growth Factor Receptor 2-Amplified Metastatic Bladder Cancer(2023) JR, Nildevande F. Lima; SAMPAIO, Luana A. F.; XAVIER, Camila B.; MATTEDI, Romulo L.; QUEIROZ, Marcelo A.; NAHAS, Willian C.; JARDIM, Denis L.
- Does displacement of lower pole stones during retrograde intrarenal surgery improves stone-free status? A systematic review and meta-analysis(2023) SANTANA, Roberto Nogueira; PORTO, Breno Cordeiro; PASSEROTTI, Carlo Camargo; ARTIFON, Everson Luiz de Almeida; OTOCH, Jose Pinhata; CRUZ, Jose Arnaldo Shiomi daPurpose: Kidney stones are one of the most common urological diseases worldwide. The size and location of the stone are the most important factors in determining the most suitable treatment options. The aim of this review was to evaluate the displacement of lower pole stones. Methods: Three studies assessing the efficacy of translocating kidney stones from the lower pole of the kidney to other locations during retrograde intrarenal surgery published in the last 20 years were included. A systematic search was conducted in the PubMed, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), and Web of Science databases using the following search terms: ""Lower pole,"" ""Lithotripsy."" Meta-analysis was performed using Review Manager version 5.4. Results: Stone-free rates were improved through displacement (odds ratio - OR = -0.15; 95% confidence interval-95%CI -0.24--0.05; p = 0.002; I2 = 21%), but at the cost of increased surgical duration (mean difference = -12.50; 95%CI -24.06--0.95; p = 0.03; I2 = 94%). Although this represents a potentially negative outcome, the improvement in clearance rates justifies the additional investment of time and effort. Conclusion: Displacement of lower pole kidney stones for subsequent lithotripsy brings significant benefits in terms of stone-free rate, with no difference in laser energy usage. However, it results in increased surgical time. Despite these factors, the benefits to patients undergoing the procedure are substantial.
- Use of artificial intelligence for sepsis risk prediction after flexible ureteroscopy: a systematic review(2023) ALVES, BEATRIZ MESALIRA; BELKOVSKY, MIKHAEL; PASSEROTTI, CARLO CAMARGO; ARTIFON, EVERSON LUIZ DE ALMEIDA; OTOCH, JOSÉ PINHATA; CRUZ, JOSÉ ARNALDO SHIOMI DAABSTRACT Introduction: flexible ureteroscopy is a minimally invasive surgical technique used for the treatment of renal lithiasis. Postoperative urosepsis is a rare but potentially fatal complication. Traditional models used to predict the risk of this condition have limited accuracy, while models based on artificial intelligence are more promising. The objective of this study is to carry out a systematic review regarding the use of artificial intelligence to detect the risk of sepsis in patients with renal lithiasis undergoing flexible ureteroscopy. Methods: the literature review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The keyword search was performed in MEDLINE, Embase, Web of Science and Scopus and resulted in a total of 2,496 articles, of which 2 met the inclusion criteria. Results: both studies used artificial intelligence models to predict the risk of sepsis after flexible uteroscopy. The first had a sample of 114 patients and was based on clinical and laboratory parameters. The second had an initial sample of 132 patients and was based on preoperative computed tomography images. Both obtained good measurements of Area Under the Curve (AUC), sensitivity and specificity, demonstrating good performance. Conclusion: artificial intelligence provides multiple effective strategies for sepsis risk stratification in patients undergoing urological procedures for renal lithiasis, although further studies are needed.
- Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer(2023) SANTOS, Gabriel Arantes dos; CHATSIRISUPACHAI, Kasit; AVELAR, Roberto A.; MAGALHAES, Joao Pedro deIntroductionUnderstanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.ResultsWe found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns.ConclusionWe identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.
- The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer(2023) CAMARGO, Juliana A.; VIANA, Nayara I.; PIMENTA, Ruan; GUIMARAES, Vanessa R.; SANTOS, Gabriel A. dos; CANDIDO, Patricia; GHAZARIAN, Vitoria; ROMAO, Poliana; SILVA, Iran A.; BIRBRAIR, Alexander; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; TRARBACH, Ericka B.; REIS, Sabrina T.Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.
- Impact of COVID-19 on surgical procedures for stress urinary incontinence in the Brazilian public health system(2023) FORNARI, Alexandre; TOLEDO, Luis Gustavo Morato; CANALINI, Alfredo Felix; BRANDAO, Thulio Bosi Vieira; ANZOLCH, Karin Marise Jaeger; FERNANDES, Roni de Carvalho; JR, Jose de Bessa; GOMES, Cristiano MendesIntroduction and hypothesisThe objective was to characterize the impact of the COVID-19 pandemic on the surgical treatment of female stress urinary incontinence (FSUI) in Brazil.MethodsThis study was conducted with population-based data from the Brazilian public health system database. We obtained data on the number of surgical procedures for FSUI in 2019 (before the coronavirus disease [COVID-19] pandemic), 2020, and 2021 (during the pandemic) in each of the 27 Brazilian states. We included official Brazilian Institute of Geography and Statistics (IBGE) data on the population, Human Development Index (HDI), and annual per capita income of each state.ResultsA total of 6,718 surgical procedures for FSUI were performed in the Brazilian public health system in 2019. The number of procedures was reduced by 56.2% in 2020, and an additional reduction of 7.2% was seen in 2021. The distribution of procedures by state showed important differences, ranging from 4.4 procedures/1,000,000 inhabitants in Paraiba and Sergipe to 67.6 procedures/1,000,000 inhabitants in Parana (p<0.01) in 2019. The number of surgical procedures was higher in states with a higher HDI (p=0.0001) and per capita income (p=0.042). The decrease in the number of surgical procedures affected the whole country and its rate did not correlate with HDI (p=0.289) or per capita income (p=0.598).ConclusionThe impact of the COVID-19 pandemic on the surgical treatment of FSUI in Brazil was significant in 2020 and persisted in 2021. Access to surgical treatment of FSUI varied according to geographic region, HDI, and per capita income, even before COVID-19.
- The Distensibility of the Human Vena Cava and Its Importance to In Vitro Studies of Venous Compression Syndromes: A Search for a Suitable Polymer for 3-Dimensional Printing(2023) PUECH-LEAO, Pedro; TORRES, Inez O.; SILVA, Erasmo S. da; CESTARI, Ismar N.; CESTARI, Idagene A.; ROSA, Jhenyfer M. da; NAHAS, William C.; LUCCIA, Nelson DeBackground: Venous compression syndromes are clinical conditions in which the large veins are compressed by other anatomical structures. Laboratory simulations may help us better understand the hemodynamics in venous compressions by creating situations similar to those seen in vivo. The aim of this study is to produce a model of the caval bifurcation using a polymer with distensibility similar to the human vena cava. Methods: Fragments of the inferior vena cava were collected from 13 deceased kidney donors (aged 15-37 years) and were tested for deformation (strain) when subjected to distension at 50 N/cm2. Strips of 5 different polymers-thermic polyurethane and Agilus30 with Vero Magenta (AV) (in 3 different hardnesses) and silicone-were subjected to the same biomechanical tests and compared with the vena cava. A model of the caval bifurcation was produced with 3-D printing. Results: The deformation (strain) of the vena cava wall was 0.16 & PLUSMN; 0.9 when submitted to stress close to 50 N/cm2. Silicone showed a strain higher than the standard deviation of venous fragments. The strain of AV resin 95 Shore was lower than the standard deviation of the venous fragments. AV Resins 70 and 85 Shore showed strains within the standard deviation of the venous specimen, with 70 Shore being closest to the mean venous strain. Therefore, this material was selected for modeling the caval bifurcation. The computed tomography scan image generated a computer model of the caval bifurcation and was printed in 3 dimensions. In addition, the segments of 2 adjacent vertebrae were also printed to reference the compression site. Conclusions: The 3-D printing of large veins can produce models with anatomy and biome-chanics similar to those of human veins and opens a field of investigation into the hemody-namics of venous compression syndromes. Polymers with Shore A70 appear to have biomechanical properties similar to those of the vena cava wall. The model obtained in this study can be used in several in vitro studies of May-Thurner Syndrome.
- The use of statins is related to a lower PSA level after endoscopic enucleation of the prostate with holmium laser (HoLEP) for the treatment of BPH(2023) SUARTZ, Caio Vinicius; BRAZ, Natalia Doratioto Serrano Faria; ANJOS, Gabriel Carvalho dos; REIS, Sabrina Thalita dos; NAHAS, William Carlos; ANTUNES, Alberto AzoubelObjectiveTo determine the factors that may be associated with a 2-month high baseline level of Total Prostatic Specific Antigen (PSA) after endoscopic enucleation of the prostate with Holmium Laser (HoLEP).Materials and methodsRetrospective study of a prospectively collected database of adult males undergoing HoLEP at a single tertiary institution from September 2015 to February 2021. Pre-operative epidemiological, clinical characteristics and post-operative factors were analyzed and a multivariate analysis was performed to determine factors independently related to PSA decline.ResultsA total of 175 men aged 49-92 years with a prostate size ranging from 25 to 450 cc underwent HoLEP, and after excluding data from patients due to loss of follow-up or incomplete data, 126 patients were included in the final analysis. The patients were divided into group A (n = 84), which included patients with postoperative PSA nadir lower than 1 ng/ml, and group B(n = 42), with postoperative PSA levels greater than 1 ng/ml. In the univariate analysis there was a correlation between the variation of the PSA value and the percentage of resected tissue (p = 0.028), for each 1 g of resected prostate there was a reduction of 0.104 ng/mL, furthermore there was a difference between the means of age of group A (71.56 years) and group B (68.17 years) (p = 0.042). In the multivariate analysis, the use of statins and lower postoperative PSA levels (p = 0.024; HR = 3.71) were correlated.ConclusionsOur results indicate that PSA after HoLEP is correlated with patient's age, the presence of incidental prostate cancer, and the use of statins.
- Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model(2023) PIMENTA, Ruan; CAMARGO, Juliana A.; GONCALVES, Guilherme L.; GHAZARIAN, Vitoria; CANDIDO, Patricia; GUIMARAES, Vanessa R.; ROMAO, Poliana; CHIOVATTO, Caroline; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; NAHAS, William C.; LEITE, Katia R.; PESSOA, Ana Flavia Marcal; VIANA, Nayara I.; REIS, Sabrina T.BackgroundPreviously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia.Methods and resultsIn vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 & mu;g/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation.ConclusionOur results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.
- Brazilian Expert Consensus for NTRK Gene Fusion Testing in Solid Tumors(2023) MACEDO, Mariana Petaccia de; NASCIMENTO, Ellen Caroline Toledo; SOARES, Fernando Augusto; SANTINI, Fernando Costa; COSTA, Felipe D'Almeida; CUNHA, Isabela Werneck da; MUNHOZ, Rodrigo Ramella; MARCHI, Pedro De; JORGE, Thiago William Carnier; LEITE, Katia Ramos MoreiraOncogenic neurotrophic tropomyosin receptor kinase gene fusions occur in less than 1% of common cancers. These mutations have emerged as new biomarkers in cancer genomic profiling with the approval of selective drugs against tropomyosin receptor kinase fusion proteins. Nevertheless, the optimal pathways and diagnostic platforms for this biomarker's screening and genomic profiling have not been defined and remain a subject of debate. A panel of national experts in molecular cancer diagnosis and treatment was convened by videoconference and suggested topics to be addressed in the literature review. The authors proposed a testing algorithm for oncogenic neurotrophic tropomyosin receptor kinase gene fusion screening and diagnosis for the Brazilian health system. This review aims to discuss the latest literature evidence and international consensus on neurotrophic tropomyosin receptor kinase gene fusion diagnosis to devise clinical guidelines for testing this biomarker. We propose an algorithm in which testing for this biomarker should be requested to diagnose advanced metastatic tumors without known driver mutations. In this strategy, Immunohistochemistry should be used as a screening test followed by confirmatory next-generation sequencing in immunohistochemistry-positive cases.
- Reply by Authors(2022) GUGLIELMETTI, G. B.; ANJOS, G. C. Dos; SAWCZYN, G.; RODRIGUES, G.; CARDILI, L.; CORDEIRO, M. D.; NEVES, L. C. O.; PONTES JUNIOR, J.; FAZOLI, A.; COELHO, R. F.; SROUGI, M.; NAHAS, W. C.
- Reply by Authors(2022) PERRELLA, R.; VICENTINI, F. C.; PARO, E. D.; TORRICELLI, F. C. M.; MARCHINI, G. S.; DANILOVIC, A.; BATAGELLO, C. A.; MOTA, P. K. V.; FERREIRA, D. B.; COHEN, D. J.; MURTA, C. B.; CLARO, J. F. A.; GIUSTI, G.; MONGA, M.; NAHAS, W. C.; SROUGI, M.; MAZZUCCHI, E.
- True open access to urological science at the International Brazilian Journal of Urology(2023) GOMES, Cristiano Mendes; REIS, Leonardo O.
- Varicocele-Associated Infertility and the Role of Oxidative Stress on Sperm DNA Fragmentation(2021) WOOD, Guilherme Jacom Abdulmassih; CARDOSO, Joao Paulo Greco; PALUELLO, Davi Vischi; NUNES, Thiago Fagundes; COCUZZA, MarcelloVaricocele has been extensively described and studied as the most important reversible cause of male infertility. Its impact on semen parameters, pregnancy rates, and assisted reproductive outcomes have been associated with multifactorial aspects, most of them converging to increase of reactive oxygen species (ROS). More recently, sperm DNA fragmentation has gained significant attention and potential clinical use, although the body of evidence still needs further evolution. The associations between sperm DNA damage and a variety of disorders, including varicocele itself, share common pathways to ROS increase. This mini-review discusses different aspects related to the etiology of ROS and its relation to varicocele and potential mechanisms of DNA damage.